Sulfide and Methane production in humans : FBO connection ?

This is a very speculative post.
It is said that in the HUMAN MICROBIOME, that people tend to be either :
Sulfate reducers (so, sulfide producers)
or
Methane producers

It's not clear how much is known about the microbiome but the word seems to be the population is split 50/50 being either dominant in Methane or Sulfide producer.

It would be interesting to see if those who identify with FECAL BODY ODOR and the spectrum including fart, raw cabbage etc tend to be in the SULFATE REDUCER group.
Nothing has shown up in Ubiome results yet, or at least what I have seen.

Methane in humans would tend to be produced by Archaea microbes, which funnily have been suggested as a potential TMAU therapy (they would break down TMA).

Sulfide producers would probably be mostly due to DESULFIBRIVIO bacteria, but possibly other sources.

It seems odd that in 2018 humanity still doesn't seem to have documented what cause stool smells exactly. Good guesses can be made but there seems to be no consensus and few papers.   

Get new posts by email

Read More

By sysbodyodor

fecal body odor, gut dysbiosis

No comments

TMAU : Choline status should be tested

Campaign.
TMAU test protocol.
Add CHOLINE status as part of a 'TMAU profile screen'. 
Who to campaign to : National Health Systems.
My hope of success : currently about 5% ?

Currently those who think they have TMAU (trimethylaminuria) do the TMAU clinical test (the urine test). This tests levels of trimethylamine and it's oxide (TMAO).

It is known that choline is closely associated with TMAU. The theory is choline gets changed to TMA in the gut. This makes me wonder if TMAU people may often have a natural blood choline deficiency despite taking choline.

Choline currently seems to have a quasi status as an essential nutrient, Probably in time it will be regarded essential. It seems to be a good emulsifier of fats in the liver. This makes me wonder if TMAU people may be naturally prone to non-alcoholic fatty liver.

Many 'normal' people have NAFL, but it would be interesting to see what the % was in TMAU people. Maybe it will turn out low choline plasma is a cause.

Targeted TMAU profiles tests :
So my first 3 tests for a TMAU profile test would be :
TMAU urine test (I would do DNA test as well).
Choline plasma test.
Liver ultrascan (to look for NA- fatty liver)

---

Other speculative tests I can think of  (quickly written) :

Very speculative other tests for a TMAU profile :
Leaky gut test.
Ethanol test (to detect candida). Now no longer available (from Biolab UK).
Microbiome stool DNA test.
Biotin test (as I was once deficient in biotin).

I would add many others, but perhaps the first 3 are a realistic aim to convince conservative metabolic consultant for a TMAU profile.

Re ethanol test.
This was a test done by Biolab UK where you had to attend the lab. Ethanol is proposed as being generated only by yeast in humans.
I see now they have discontinued it, and refer people to do microbe organic test by Great Plains, which I don't think is as accurate (or at least, not a decade ago).  

Ultimate biochemical test for Systemic Body Odor :
A broad screen of volatiles known to cause systemic body odor. Currently they don't know the list of volatiles, so at this time this would be EXPLORATORY.
Once it was known what volatiles cause systemic body odor, they could then create a profile test with these volatiles.
Likely suspect volatiles (my guess) : dimethylsulfide, dimethyldisulfide, trimethylamine (small player).

Get new posts by email

Read More

By sysbodyodor

campaign, gut dysbiosis, metabolic malodor, metabolic/systemic malodor, systemic body odor, systemic malodor syndrome, tmau test, trimethylaminuria

No comments

marine trimethylamine : a big source of greenhouse gas methane

It seems that trimethylamine produced in marine environments is often broken down to methane.
Methane is a main gas that cause the 'greenhouse effect' (Global warming).
Perhaps this is another reason for scientists to look at ways to block TMA formation.
Which in turn could lead to a therapy for human gut TMA formation.

TMA produced in marine environments : 
I only heard of this TMA connection. Probably marine microbes produce TMA. Apparently the TMA is broken down to methane, which is a major part of the gases that cause global warming.

I have tried to look for the % stats for sources of greenhouse gases, but not been too successful.
One site said

% methane makes up greenhouse gases : 16% (2nd after CO2).
% of NATURAL methane sources are marine : 88% (78% wetlands, 10% sea).
This does not include HUMAN sources (e.g. petrol, coal, farming).

I would guess the marine TMA is a by product of microbe fermentation, which then is broken down to methane. Ironically this has been suggested as a possible therapy for TMAU, in that some microbes would break down the TMA in the gut. I guess so few are thought to have TMAU it would not add much to the total world methane output.

But ... this means it's in the world's interest to find TMA blockers, so that TMA does not produce methane. This would probably mean interfering with the enzyme that produces TMA. Antibiotics are often 'microbe enzyme inhibitors', so it's much the same thing as antibiotics.

So maybe there is research going on to prevent methane formation from TMA to save the planet.

3 main ways TMA could be inhibited or broken down (I know of) :

1. Interfering/inhibiting the microbe enzyme that produces TMA (antibiotics often work this way).
2. 'Drugging the relevant microbes'. This seems to be the Cleveland method. They are tricking the microbes into working on a compound that is like choline but much more dificult for them to breakdown.
3. Use microbes to break TMA down via the methane pathway. Some microbes have enzymes that can break TMA down.

My thoughts on TMAU and systemic body odor
Any therapy that inhibited TMA formation or broke down TMA (e.g. to methane) would be good for anyone who thought their smell(s) were solely created by TMA. I am a bit sceptical that TMA is the only source of smells for most, so a bit worried such a therapy would not have the expected benefits. But I may be wrong.

Acronynms :
TMA : trimethylamine
TMAU : trimethylaminuria

Note :
graph and stats may be incorrect.
    

Get new posts by email

Read More

By sysbodyodor

gut dysbiosis, metabolic malodor, metabolic/systemic malodor, possible future therapy, systemic body odor, TMAU research

No comments

Bacteroidetes don't produce trimethylamine from choline

 2012 paper suggests bacteroidetes phyla are poor at degrading choline to trimethylamine.
Firmicutes, Actinobacteria, and Proteobacteria can produce TMA.
Ubiome suggest Firmicutes make up 60% of normal flora, Bacteroidetes 30%.
My own Ubiome results average (of 4) were Firmicutes 70%, Bacteroidetes 26%.
My own opinion, not enough known of the gut flora for me to have an opinion.
This post more a 'for your information' post, rather than any 'breakthrough'.
Perhaps others should try stool DNA testing.

The new Phillips/Shephard TMAU-FMO3 overview paper mentioned a 2012 paper which they seemed to have great credence for. The research in the paper proved TMA could be produced from choline by certain gut bacteria flora phyla (Firmicutes, Actinobacteria, and Proteobacteria) but not from Bacteroidetes.

Quote from Phillips/Shephard/Fennema paper

Free choline is absorbed throughout the small intestine and is subsequently integrated into cell membranes or actively taken up by the liver, where it can be converted to betaine, phosphocholine, or lecithin (Zeisel, 1990). High amounts of choline may exceed the absorptive capacity and pass through to the large intestine, however, where it is metabolized to methylamines by microbial action (Zeisel et al., 1983). Choline is a quaternary ammonium compound containing a trimethylammonium moiety. Thus, it can act as a precursor for TMA (Zeisel et al., 1989; Chalmers et al., 2006). The bacterial conversion of choline to TMA involves the cleavage of the carbon-nitrogen bond of choline, producing TMA and acetaldehyde (Hayward and Stadtman, 1959). Craciun and Balskus (2012) proposed that a glycyl radical enzyme CutC (EC 4.3.99.4), encoded by the bacterial choline utilization gene cluster (cut), might act as a choline TMA-lyase to catalyze this initial step in choline degradation (Fig. 1). This was confirmed by demonstrating that deletion of cutC in Desulfovibrio desulfuricans abolished the ability of the organism to produce TMA from choline. Bioinformatics analysis revealed cutC homologs in 89 bacterial genomes. The homologs are not distributed evenly among the major bacterial phyla of the human gut, being present in Firmicutes, Actinobacteria, and Proteobacteria spp. but absent from Bacteroidetes (Craciun and Balskus, 2012). Table 1 shows bacteria known to be associated with formation of TMA via choline degradation.

This is the paper they refer to :
Microbial conversion of choline to trimethylamine requires a glycyl radical enzyme

Firmicutes and Bacteroidetes seem to make up the bulk of the gut flora. There seems to be different opinions on what that % make-up should be for a healthy gut.

Ubiome suggest the healthy gut should have about 70% Firmicutes and 30% Bacteroidetes.

My own Firmicute/Bacteroidetes ratio :
I have tested with Ubiome 4 times.
In 3 samples my Firmicute was slightly higher than normal. Bacteroidetes was slightly lower.

My view on the knowledge of the human gut flora :
I would suggest if you compare it to the history of USA, it may be around the year 1620. Perhaps I'm wrong, but my impression is so little is understood of the gut flora (Oct 16). I'm hoping technology has caught up and we will be at around year 1900 in the next few years.

My view on my own results :
I will not be excitedly trying to alter my firmicute/bacteriodetes ratio, though may look around for info. It seems that bacteroidetes are not the type usually put in 'probiotics'. Possibly partly as they are so 'sensitive' (and die easy in oxygen). Possibly there is no 'bacteroidetes' probiotic on the market. The general view seems to be taking 'prebiotics' is the best hope of feeding bacteroidetes.

Perhaps others can do the stool DNA test :
Since the stool  DNA test is relatively cheap, and sometimes they do special offers (e.g. 3 for 1), perhaps others with systemic body odor/halitosis can do the test and mention anything they want about the results in the comment section of this post.

Stool DNA test suppliers :
Ubiome (choose citizen science)
American Gut (also 'UK Gut')

These are the 2 best known suppliers. Thankfully, they are consumer health friendly, and not health learning obstacles as is the case with normal DNA tests, urine tests etc. The spirit of the testing would be that it may be not very useful, but perhaps will be in hindsight.    

What's this to do with systemic body odor ?
My own view is that most cases of SBO are probably due to enzyme weaknesses, probably the bulk of which are due to sub-par FMO3 enzyme function. But I also think gut dysbiosis will be a common factor in 'FMO3 body odor', probably as part of the syndrome, and perhaps often the 'tipping point'.

Currently TMAU is the only acccepted form of systemic body odor. My own view is that 'FMO3 body odor' can mean smelling of any FMO3 substrate rather than just TMA, and many of the volatiles produced in the gut are probably FMO substrates. Although this paper was about TMA, perhaps bacteroidetes can't produce other FMO3 substrates, but who knows.

Get new posts by email

Read More

By sysbodyodor

fecal body odor, gut dysbiosis, metabolic/systemic malodor, my results, possible future therapy, stool dna, systemic body odor, systemic malodor syndrome, TMAO-CVD, tmau, TMAU research

2 comments

P&G TMA-blocker will be stronger than DMB

In a magazine article in April about the gut flora, this statement was made

"Hazen says DMB, the olive-oil molecule from his study, is too weak to put into a pill. He’s working on creating stronger inhibitors."

So it looks like something stronger than DMB will be used by the Cleveland Clinic for their 'TMA-blocking supplement' which will be marketed as an over-the-counter product sometime in the future by Proctor & Gamble.

Full article : Statnews April 2016

DMB : 3,3 di-methyl-1-butanol (wikipedia)
DMB is of interest to the TMAU community as it's been shown to block the formation of trimethylamine in the gut (of mice) by gut flora. It's naturally present in olive oil, balsamic vinegar etc.

TMA-oxide and atherosclerosis theory (wikipedia)
In 2011 Dr Hazen et al at the Cleveland Clinic put forward a theory that tma-oxide may be a factor (perhaps main factor) in the development of atherosclerosis. Since then the lab has been researching this and putting many papers forward to enforce this. In 2015 they said that DMB was an inhibitor of TMA in the gut of mice.

Analogs
Quite often an approach in humans to damage is to find an 'inhibitor' which stops a damaging checmical reaction. in the 'TMA precursor (choline etc) -- TMA -- TMA-oxide' cycle of reactions, the aim is to block TMA formation. 'Inhibitors' or often refered to as Analogs, and in this case they found that DMB is an inhibitor of TMA formation (from choline etc).

Better inhibitor than DMB
So it seems they are looking at stronger inhibitors than DMB to put in the P&G 'supplement'. The final product will not be a 'DMB pill'. This is even better news I guess. A heart-disease expert recently reviewed the evidence on the 'TMAO- atherosclerosis' theory and estimated that perhaps 10-20g of DMB (in divided doses) would be needed to block TMA in the gut. But something better than DMB is even better.

Possible 'resistance' like antibiotics ?
One potential 'danger' pointed out is that the article seems to say that the DMB probably alters the gut flora composition, which might mean 'immune' bacteria then become dominant. Very much like antibiotic drug resistance. DMB is not lethal to gut flora like antibiotics, but nevertheless the same resistance may occur due to flora composition change.

Good news for Trimethylamiuria people
Obviously blocking TMA formation in the gut is great news for those with TMAU. First documented in 1970, up until this interest in 'TMAO-atherosclerosis' there has been almost no interest in TMA metabolism in humans. Now suddenly TMA metabolism in humans is of main interest in human health research.

My view (in terms of systemic body odor) :
A 'TMA-blocker' pill sold over-the-counter by Proctor & Gamble will definitely happen. Anyone who thinks trimethylamine is the sole cause of their systemic malodor should regard this as possible a very good therapy for 'TMAU'. But personally I feel TMA may not be the only volatile that causes what I call 'FMO3 smells', so I am a bit worried. But maybe TMA is a main factor (indirectly) and blocking TMA may relieve the pressure on FMO3 (for example). Anyhow, I will definitely be trying it and could be regarded a 'banker' hopeful therapy that will happen while we worry about other hopes.
 

---

Get new posts by email

---

Read More

By sysbodyodor

DMB pill, gut dysbiosis, metabolic malodor, metabolic/systemic malodor research, possible future therapy, systemic body odor, TMAO Research

5 comments

How much DMB for TMAU ?

What daily dosage of DMB should a TMAU patient take to block TMA formation in the gut each day ?

Answer (estimate, in theory) : about 10-20g DMB a day (divided into doses) 

About this answer :
This is an estimate by a very respected CVD expert in a recent overview paper of the TMA-oxide - atherosclerosis connection proposed by Hazen et al in 2011.

Answer is based on Mouse studies for atherosclerosis :
The answer is not based on humans taking DMB as trials have not reached that stage. It is an estimate based on extrapolating the dosage given in mice studies. So you could say it is a 'expert estimate based on mouse studies' given the current info.

The estimate is generally from this overview paper : link

Acronyms

DMB :  3, 3 dimethyl-1-butanol
TMAO : trimethylamine-n-oxide
TMA : trimethylamine
CVD : cardiovascular disease
FMO3 : flavin mono-oxygenase enzyme (isoform 3)

About DMB :
DMB in this case refers to 3, 3 dimethyl-1-butanol.

Atherosclerosis and TMA-oxide theory :
Put forward by Hazen et al of Cleveland Clinic in 2011. My impression is that the theory is that TMA-oxide may be the main factor in the development of atherosclerosis.

Connection with TMAU :
Since TMAU is proposed as being a malodor caused by TMA, any research that may block TMA formation in the gut would be a potential therapy. This is an obvious target for the 'atherosclerosis researchers' to aim for. So TMAU patients should be incidental benefactors of this approach.

Where do you humans get TMA from ?
TMA is smelly so is not normally consumed by humans. Nor is it a metabolite from human metabolism. It's only real source in humans is gut flora altering certain compounds in the diet (e.g. choline, carnitine, lecithin, TMA-oxide in fish).

The 'TMA blocker' story so far :
Hazen et al lead research into the TMAO - CVD theory. In Nov 2015 they published a paper showing DMB blocks TMA formation in mice (gut).

How long until a 'TMA blocker' drug is available ?
Cleveland Heartlab have already signed a deal with Proctor & Gamble to market an 'over the counter' TMA-blocker drug. It is not known when this will be available. I am currently presuming it may be DMB based, but perhaps they will find an even better 'TMA-blocker'.  

How can you get DMB now ?
DMB is a natural compound in things like balsamic vinegar, olive oil, red wine etc. I do not know how much you would need to take to get 10-20g daily of DMB. My own view is that these foods are probably bad for people with FMO3 issues, as they will likely contain many other FMO3 substrates that may end up causing smells (probably indirectly after being altered by gut flora).          

My own view :
I am very optimistic about a 'TMA-blocker'. But my own belief is that people with an FMO3 issue probably smell of all FMO3 substrates and not just TMA. So that concerns me but I am still optimistic. Also FMO3/TMAU was a very neglected disorder, but now TMA metabolism in humans is on the center of radars for atherosclerosis researchers. I will certainly buy DMB when available. If I thought TMA was the only malodor problem I would be ecstatic.

It also shows how TMAU/FMO3 has been a neglected disorder, as this therapy is an obvious concept which was never looked at for TMAU. Now that it is proposed to be connected with CVD we can expect lots of research into TMA metabolism.

My feelings on this (in tags) in relation to metabolic/systemic malodor :
optimistic, excited, cautious, research leads could appear from anywhere now, TMA metabolism is on the radar bigtime.

---

Get new posts by email

---

Read More

By sysbodyodor

DMB pill, gut dysbiosis, Hazen TMAO research, metabolic/systemic malodor research, possible future therapy, research, systemic body odor, systemic malodor syndrome, TMAO Research, TMAO-CVD, tmau

1 comment

2nd batch ubiome results : fecal body odor

This is my 2nd batch of my Ubiome microbiome dna results.
I don't see anything that may be a biomarker for 'fecal body odor'.
But I don't know how to interpret the results.
And also the technology and understanding of the microbiome is at an early stage.
I still think microbiome testing is worthwhile (as it's so cheap)

2nd batch of Ubiome results :
I tested before in 2014. This new batch of 3 was part of their Xmas offer '3 for price of 1'. I have only briefly looked at the results.

Note :
These are just 4 examples of the data given in Ubiome results.

Fecal Body Odor / FMO3 malodor
I reckon FBO is caused by FMO3 substrates, so I tend to look out for anything to do with FMO3 substrates in the results.

FBO and dysbiosis :
I think gut dysbiosis goes naturally with 'Fecal Body Odor' (a syndrome). My question is  :
Do people with FBO have a particular gut dysbiosis ? or
Do those with FBO have general gut dysbiosis ?
This is where I think microbiome testing will be very useful, but perhaps the understanding is at too early a stage.

My interp of my results :
I can't make much of it.

Of initial interest is :
Secondary metabolite biosynthesis.
Flavone and flavonol biosynthesis 0.7X
Flavonoid biosynthesis

I mention these 2 as they were low and the word 'flavone' is maybe associated with Vitamin B2 and/or flavin enzymes ? Maybe not.

Closing remarks :

Next time I might try using 'American Gut' purely as they are a different lab.

I suggest doing these tests even though they currently may not give us any relevant info, mainly as they are the right way to go and they are cheap.

Sometimes Ubiome do special offers 3 for 1 etc.

What do I think causes 'Fecal Body Odor' :
I think the smells are probably mostly sulfides, and some amines, of a certain structure (soft nucloephilic) that are probably naturally oxidized mainly by FMO3 enzyme.
My theory is :
The person will have a weakness of some % of the FMO3 enzyme
They will tend to a certain or common gut dysbiosis, exacerbating the problem due to overload.

---

Get new posts by email

---

Read More

By sysbodyodor

Body Odor, fecal body odor, fmo3, gut dysbiosis, metabolic malodor, my results, stool dna

No comments

New Hazen paper : Fecal transplant mice get TMAO artherosclerosis

A recent theory suggests TMA-oxide may cause atherosclerosis. TMA-oxide is oxidized trimethylamine. Hence a therapy is likely to try and reduce or neutralize TMA levels produced in the gut

New paper from Dr Stan Hazen et al re TMA-oxide and CVD  :  Fecal transplants in mice

Dr Stan Hazen research has often been reported here as since around 2011 his lab has suggested a strong connection between TMA-oxide plasma levels in humans and risk of atherosclerosis (CVD). This research may have an added benefit to metabolic malodor sufferers who feel trimethylamine is the sole cause of their malodor, as any resulting therapy may mean neutralizing or blocking TMA production in the gut, thus the person will absorb no TMA into their bloodstream.

Fecal transplant in mice to give them atherosclerosis
In this paper they seemed to use 2 strains of lab mice and gave their fecal transplant microbes to a strain of mouse that was microbe free in the gut. One strain of mouse seems to have a high TMAO 'flora', whereas the other does not. It seems that the transfer of the feces from the high-TMAO producing mouse caused the donor mouse to develop CVD. So they seem to be saying risk of CVD is highly likely to be due to a TMA rich gut flora and when they transfered this flora to a mouse with no gut flora, the mouse then developed CVD.

This seems to be more evidence for the TMAO-CVD connection theory, though I guess it is still a theory to be given a consensus in the CVD research community.

The paper says at the end :
Gut microbes may thus represent a novel therapeutic target for modulating atherosclerosis susceptibility.

So they are suggesting that altering a TMA rich gut flora should reduce the chance of CVD, but also for the TMAU community it should mean reducing or negating or blocking TMA in the gut, possibly by altering the gut flora. This may lead to anti-TMA probiotics, for example. It is also very likely that research will be done to see which microbes generate TMA in the gut.    

     

---

Get notified of new posts by email
Join the email list via the sidebar

---

Read More

By sysbodyodor

fecal body odor, gut dysbiosis, Hazen TMAO research, metabolic malodor, possible future therapy, research, systemic body odor, systemic malodor syndrome, TMAO-CVD, TMAU research

No comments

New TMAU paper : Archaea neutralise TMA in the gut

About : New paper that says that archaea microbes neutralise trimethylamine in the gut. In future perhaps 'archaeabiotic' treatment will help people with TMAU and perhaps do away with the need for diet control etc.

This is a paper about the possible role of archaea microbes in neutralising trimethylamine in the gut. Archaea are methane producing organisms common in many people guts but not all. In the microbe breath test, some people are shown to be methane producers as well as hydrogen producers, whereas some are just hydrogen producers. It seems that archaea produce this methane.

The paper says that perhaps in the future people with TMAU may be able to use an 'archaebiotic' to in effect 'neutralise' trimethylamine in the gut. This would be in practice a 'cure' for TMAU, but anyone with a FMO3 deficiency would still have that deficiency.

Full paper : Archaea and the human gut: New beginning of an old story Link to full paper

My view on this :
This is very good news. If something can neutralise TMA in the gut then there is no TMA going to the liver. It neutralises the TMA load. However the person still has an FMO3 deficiency if they are TMAU1. For those who feel they only smell of trimethylamine, it is in effect a working cure I guess. However FMO3 oxidizes many sulfides and amines in humans, and I believe that most people with an FMO3 issue smell of other sulfides and amines mostly, and it would not seem to be a cure for that. Not unless it also neutralises those volatiles too.

Overall though it is a very positive step and the 'archaeabiotic' would be a natural solution rather than taking a drug.  

---

Get notified of new posts by email
Join the email list via the sidebar

---

Read More

By sysbodyodor

gut dysbiosis, metabolic malodor, possible future therapy, research, TMAU research

No comments

2 new papers by Dr Hazen re TMA-oxide and heart disease

Dr Stanley Hazen et al at the Cleveland Clinic continues to release research papers on his TMA-oxide and coronary vascular disease connection at a rapid pace. Dr Hazen et al first proposed the CVD-TMAO connection around 2011. Today 2 new papers are released.

Relevance to metabolic/systemic malodors : 
I currently think FMO3 overload/deficiency is the main cause of 'metabolic malodors'. FMO3 enzyme oxidizes many sulfides and amines. Dr Stanley Hazen in 2011 suggested there is connection between TMA-oxide levels and atherosclerosis. This has led to much research into FMO3 and trimethylamine whereas FMO3 and TMAU were previously almost completely neglected.

First paper :
The first looked at 720 patients with stable Heart Failure over 5 years and checked to see if there was a TMAO and CVD connection

CONCLUSIONS:
High TMAO levels were observed in patients with HF, and elevated TMAO levels portended higher long-term mortality risk independent of traditional risk factors and cardiorenal indexes.
Paper : Prognostic value of elevated levels of intestinal microbe-generated metabolite trimethylamine-N-oxide in patients with heart failure: refining the gut hypothesis.: Pubmed link

2nd paper :
The 2nd paper looked 112 heart failure patients and checked them for TMAO, choline and betaine levels to see if there might be a connection..

CONCLUSION:
Elevated plasma TMAO, choline and betaine levels are each associated with more advanced left ventricular diastolic dysfunction and portend poorer long-term adverse clinical outcomes in chronic systolic HF. However, only higher plasma TMAO levels was associated with poor prognosis after adjustment for cardio-renal indices.
Paper : Intestinal Microbiota-Dependent Phosphatidylcholine Metabolites, Diastolic Dysfunction and Adverse Clinical Outcomes in Chronic Systolic Heart Failure : Pubmed link

What the Hesart Disease expert community think about TMAO in relation to CVD
I guess the 'TMAO-CVD connection is a new theory and it will take time to see if a consensus is reached whereby TMAO is regarded a/the major heart disease biomarker. At the moment I guess they need to 'convince' the heart disease expert establishment.

It's relevance to metabolic/systemic malodors
For someone who feels that TMAU completely explains their metabolic malodor, since they are likely to come up with a trimethylamine-blocker drug ( a drug that will block bacteria enzymes from converting choline and betaine to trimethylamine, it would in effect mean a cure for TMAU. Those with 'genetic TMAU' would still have the FMO3 fault but there would be no TMA produced in the gut.

However I feel that for most people trimethylamine is not the only source of malodor, and that most will have problems with all compounds that use FMO3 to be oxidized. This may mean many sulfides and amines, but probably mainly a few. So although a 'TMA-blocker' is likely to reduce the load on their FMO3 enzyme, it would not seem to be a cure to me.

But the CVD-TMAO connection means there will millions of dollars of research into understanding FMO3 now, and this is very good news. Previously FMO3 was almost completely neglected . Dr Hazen et al are likely to keep producing many more papers on the subject.

Read More

By sysbodyodor

fecal body odor, fmo3, gut dysbiosis, metabolic malodor, possible future therapy, TMAO-CVD, TMAU research

2 comments

Norwegian study about TMAO and heart failure

New paper by a group of Norwegian researchers
Study done on humans
Reinforces suggestion of connection between TMAO and Heart Diseasae
TMAO is oxidized trimethylamine
Will likely result in much more research into TMAO and trimethylamine
Might lead to a 'TMA-blocking' drug

A new research paper by a group of Norwegian researchers has reinforced the notion that trimethylamine-n-oxide may have a strong connecrion with heart disease. The researchers checked TMAO levels in patients with heart disease and healthy volunteers and assessed the outcomes. It seems they found a connection with TMAO and heart failure. One especially interesting thing about this study is that it a new group of researchers making the connection between TMAO and CVD, thus possibly reinforcing the connection the original research group made (Hazen et al) .

What does it mean for people with TMAU ?
It probably means there will be much funding and worldwide research into TMA/TMAO and possibly FMO3, and the aim will probably be to learn as much as possible about TMA/TMAO production in humans and FMO3 metabolism, and to produce cures such as a trimethylamine-formation blocking drug For anyone who thinks they have a malodor due to trimethylamine only, I guess it would mean a cure (no TMA would mean no smell ?)

My own opinion :
Personally my own current view is that I think most people with a metabolic malodor probably have 'FMO3 malodor', which means an odor from any FMO3 substrate produced in humans (including many sulfides and amines). So I am skeptical that preventing TMA production alone may be a 'cure' for 'FMO3 substrate malodor', but I hope I am wrong. They may also look at ways to alter the gut flora etc, as well as looking at FMO3 which up until this connection was neglected by research. So overall it's a very good thing for people with 'FMO3 malodors' and to anyone who thought they only had a malodor due to trimethylamine.

Read More

By sysbodyodor

Body Odor, fecal body odor, FMO3 research, gut dysbiosis, halitosis, metabolic malodor, possible future therapy, research, systemic body odor, systemic malodor syndrome, TMAU research

No comments

For first time scientists decrease trimethylamine production in gut using a drug

Melodium reduced TMA from carnitine but not choline

Scientists used Meldonium to decrease trimethylamine production from carnitine by gut microbes
Only worked on TMA produced via carnitine, not from choline
First time a scientific paper has been released that attempted to decrease TMA levels in the gut
Research is because of a paper suggesting a link between TMA-oxide levels and heart disease published 2 years ago.
Most of this type of research will be because of a potential 'heart disease' connection

Pubmed abstract : Suppression of intestinal microbiota-dependent production of pro-atherogenic trimethylamine N-oxide by shifting L-carnitine microbial degradation.
Authors : Latvian researchers

My own view 
In relation to systemic malodors, my view isthat  this may only be of use to those who feel they only have an odor due to trimethylamine, not to odors caused by other FMO3 substrates or other volatiles. Nonetheless it is great to see scientific work will be done on trying to eliminate TMA production in the gut because of a paper that suggested a connection with heart disease and TMA-oxide  

Background 
In 2012, a paper by researchers at the Cleveland Clinic suggested that there was a connection between TMA-Oxide levels produced by the gut flora in the gut, and 'heart disease' (CVD). Since then it has been very likely that scientists worldwide will be looking at ways to reduce or eliminate trimethylamine production in the gut. This seems to be the first doc
ument of a a drug being used to suppress TMA production. TMA in the gut is formed from precursors such as  choline and carnitine being degraded in the gut, and also from TMA-oxide in fish foods. In this case, the drug meldonium was recorded as decreasing TMA production by gut microbes from carnitine, but not choline.

Note about Meldonium
Currently (Oct 2014) it only seems to be available in Lithuania and Russia and is not approved (yet) by the USA FDA. Link : Wikipedia Meldonium 

What it means
First of all, it shows that labs around the world are probably researching ways to eliminate TMA production in the gut because of a theorized link with CVD. So this is probably the first of many research projects looking to inhibit TMA production in the gut. Of course this would also help anyone who thought trimethylamnine was solely to blame for their metabolic malodor

My own concerns 
Personally I think people with a 'FMO issue' will be prone to smelling of any volatile that is oxidized by the FMO3 enzyme. Perhaps trimethylamine may not even be a 'big player' in the range of volatiles they could smell of. So while I am happy about this research, I am concerned it may not solve most cases of 'FMO3 malodor', though perhaps it is not as straightforward as that.

My understanding of  FMO3
FMO3 oxidizes 1,000s of sulfides, amines and phosphate containing compounds of a certain structure generated in the body, gut, and environment. The human has quite a few 'oxidizing' enzymes, only really discovered in 1960's. Often these enzymes are regarded as part of the group of 'drug metabolizing enzymes'. Surprisingly, little is still known about them, and especially ones like FMO3 that are currently regarded as 'small players' . FMo3 may be a 'small player'(?)  but it seems a commonly used enzyme.

Read More

By sysbodyodor

fecal body odor, gut dysbiosis, metabolic malodor, possible future therapy, systemic malodor syndrome, tmau, TMAU research

No comments

My Ubiome results for fecal body odor

I did the Ubiome microbiome DNA test to see if it would give any clues to what may cause my metabolic body odor which expresses itself as bowel malodors, including fecal and gas and other malodors. My guess is that most of the malodors are caused by sulfides and amines created in the gut by the gut flora.  I have a theory that it may be a syndrome, and 'gut dysbiosis' may be part of the syndrome. Either a type of gut dysbiosis specific to metabolic bowel malodors, or a general gut dysbiosis.

I note that the Ubiome test only tests for bacteria, so will not notice fungus such as candida, or parasites.

I don't see anything much noticeable about my results that may give any clues, but I am not an expert and have only glance at the results. Perhaps in isolation they don't mean as much as they would if grouped with other 'metabolic malodor' sufferers.

My own current remarks about my results :
Lactobacillus and Bifidobacteria were much lower than the average sample
Bacteroidetes were more than averageDesulfibrivio speiec were much lower than normal (I thought this might be a culprit in 'fecal body odor'. Not ruling it out yet)

Below are more screenshots of my results. There is more details than shown in these photos. :

Notes about my graphs :
The way to judge the horizontal graphs is :
vertical black line : that's my result
vertical blue line : that's the average
orange area in line strips : I guess that means if my black line is in there then it's 'very abnormal'  

Each page here shows just the top 5 of each category. There are actually about 15 in each list.

On reflection, it seems a lot of my 'good bacteria' are much lower than normal, even though the 'very good' bacteria in a normal person make up a small % of the total microbes.

A lot of the microbes do not have any explanation yet, so I can't interpret what their result means

Overall I cannot make any conclusions yet, due to lack of knowledge and lack of info.

But I am glad I tested as it's all there currently is and retrospectively it may be vcry useful.    



So far I can't make any conclusions over my results, but hopefully over time they will be of use retrospectively or compared to other metabolic malodor results.

Read More

By sysbodyodor

fecal body odor, fmo3, gut dysbiosis, metabolic malodor, stool dna, systemic body odor, systemic malodor syndrome

1 comment

New paper on certain bacteria cause colon distenstion

I noticed this new paper which is to do with IBS, but perhaps it may someday also have a connection with what is the main complaint on body odor forums, that is 'fecal body odor' (FBO). Technically I think of FBO as 'sulfide and amine' malodor, as the smell of feces is a mix of chemical compounds. Also I think while fecal is the most embarrassing odor, the smells probably vary right across the sulfide and amine spectrum depending on which sulfides or amines are most abundantly produced by the gut flora at anytime, or even perhaps bbeing smells of other things such as hormones. FMO3 is one of a few enzymes that mainly oxidizes small sulfides and amines, which is where FMO3 would come into the equation.

Anyhow, with IBS there is not usually a complaint of systemic odors, so those with IBS and FBO must make up a small % of the IBS group and there must be some other added factor for 'FBO syndrome' (if it is a syndrome). To me the most likely added factor is under-performance of the FMO3 enzyme, making it a syndrome.

Back to the study, people with IBS often complain of a bloated abdomen. There must be a good chance this is caused by excess gas of some sort. In this research paper they seem to be blaming a sulfate-reducing bacteria and enterobacteriaceae rich gut flora for the distended abdomen, and lack of bifidobacteria..They then put this fecal microbiota into germ-free rats who then got the same distended colon, implying this gut flora conditions could be blame for IBS distended colon. Presumably more research is need.

However, to me it seems of interest to people with FBO, as a bloated abdomen is often somethign people with FBO say they have, and sulfate-reducing bacteria are often mentioned as a possible baddie in the gut flora, along with lack of bifidobacteria ( a gut bacteria 'goodie').

At this point I believe there is no understanding of 'FBO' and we need to wait until it is understood before any therapies are possible. So I don;t think trying anything due to this research will prove to be beneficial yet, as too little is understood. But nevertheless it is an interesting paper. Perhaps sampling done by companies such as Ubiome and AmericanGut will help understand the gut flora composition in those with FBO in the near future.

New medical paper : pubmed
     

Read More

By sysbodyodor

fecal body odor, fmo3, gut dysbiosis, systemic body odor

No comments

Exploring your gut microbiome

With the advances in DNA testing, it is getting possible to explore the genetics of all aspects of humans. This includes your 'microbiome', microbes which live around surface arfeas of humans, and especially is present in the gut (the gut flora). Many experts believe the by-products and metabolism of the 'gut flora' should be regarded perhaps on the same level as endocrine glands on the effect they can have on humans, or at least be regarded as a 'powewerful metabolic force'. One simple example of this is the 'accepted' diagnosis trimethylaminuria, where most of the trimethylamine is regarded as being produced by the gut flora. Many people with 'metabolic malodors' report of having a broad spectrum of malodors that are 'facel' or 'flatulent' in nature, or various other malodors that are probably sulfides and amines. These too are probably produced by the gut flora.

Over the last year 2 genetic groups have come up with a way of collecting a big database of human microbiome samples and at the same time letting the person see their own result. The 2 companies both used 'indiegogo' to start with, probably to see if there was interest. Now they both have their own sites.

The groups are:
Ubiome
and
American Gut

Both are very new concepts (in business and in testing), so should be regarded as exploratory. It is not clear what the results will tell, and should be regarded as not being useful at this point (but hopefully are).

Most people who feel they have a metabolic malodor report of 'fecal' smells, so perhaps they might have a certain pattern (for instance being rich in sulfide and amine producing bacteria).

It's all speculation at this point, but it seems an opportunity for sufferers to by-pass the orthodox medical system and show their support for 'pioneers' in health research who may otherwise be blocked by politics, and also to perhaps get some useful info on their microbiome, perhaps even in hindsight.

For those who feel they have a metabolic malodor, the option to send a fecal sample would be the choice to make. Personally I chose Ubiome.

Other links on the subject :
ubiome twitter feed
ubiome original starting place on indiegogo
americangut.org twitter feed
americangut on indiegogo

Read More

By sysbodyodor

fecal body odor, gut dysbiosis

No comments

research : Archaebiotics: Proposed therapy to prevent trimethylaminuria

What is this ? : new research paper by a group of microbiologists based in France/Ireland (main base is France) 
Who would it potentially help ? : mainly those with trimethylaminuria, but possibly it will help reduce other FMO3 substrates too.
What is the concept  ? : using a microbe that is known to be present in many human colons, that naturally alters trimethylamine in the gut to a methane compound that is inert and odorless, so reducing the absorption of trimethylamine into the bloodstream
What stage are they at ? : At the moment they have just proved the concept, and it is at it's very earliest stages

Full free paper : Archaebiotics: Proposed therapeutic use of archaea to prevent trimethylaminuria and cardiovascular disease

This is research that aims to alter the gut flora to a more friendly type for people with TMAU. It aims to 'negate' the trimethylamine formation in the gut, and so reduce the amount absorbed into to the bloodstream. They term it 'Archaebiotics' since archae is not part of the bacteria family, but it is the same concept as 'probiotics' and 'probtiotic therapy'.

I am not a great believer that 'trimethylamine' alone is the only compound to make people with a FMO3 susceptibility smell (FMO3 oxidizes 1,000s of sulfides and amines), but it may be a major factor and so reducing the TMA load is something to be welcomed. Also it may 'inactivate' other FMO3 substrates, so it may be more helpful than I expect.

I have thought of this type of therapy before and it has been previously speculated a long while ago (my own hope was FMO3 enriched probiotics) but now that a paper has been published showing a connection between trimethylamine-oxide levels and cardiovascular disease, there should hopefully be a lot of research going on worldwide now where they are trying to reduce or block trimethylamine formation in the gut.   

Read More

By sysbodyodor

gut dysbiosis, systemic body odor, TMAU research

2 comments

Osmotic laxative : Laxido was good ; Dulcobalance was bad

I was experimenting with osmotic laxatives recently. Laxido seemed to work 'perfectly', but Dulcobalance made me even more ADHD, agitated, and even constipated (with any stools being of a small amount and messy).

Here are the listed ingredients for both products :

laxido ingredients : 13.125g Macrogol 3350 ... and 350.7mg Sodium chloride, 178.5mg Sodium
hydrogen carbonate and 46.6mg Potassium chloride

dulcobalance ingredients : 10g of macrogol 4000 ... and saccharin sodium, and the orange-grapefruit flavour which contains orange and grapefruit oils, concentrated orange juice, citral, acetaldehyde, linalol, ethyl butyrate, alpha terpineol, octanal, beta and gamma hexenol, maltodextrin, gum arabic, sorbitol (E420)

I have 3 possible theories why dulobalance may have been problematic :

1. Sulfur dioxide included : This may have been the issue. Perhaps the sulfur was feeding sulfur producing bacteria or some other microbe. It says in the leaflet that some are allergic to sulfur though I do not think I am.

2. Grapefruit oils included : compounds in grapefruit are known to inhibit the CYP3A4 enzyme present in the gut of humans. This has a similar function to the FMO3 enzyme (but much more relatively 'important'). Perhaps if my gut CYP3A4 was inhibited it caused a toxic buildup. I suspect this may have been the most likely cause.

3. The size of the macrogol : The macrogol is the basic ingredient that causes osmotic laxatives to induce water into the bowel. I don't know enough to know if the different size could be an issue.

4. Lack of electrolytes : Laxido seems to add balanced electrolytes to the sachet whereas Dulcobalance doesn't add the same mix.

5. Sorbitol : Dulcobalance adds sorbitol which may have fed bacteria in the gut in a certain way when mixed with macrogol.

So in hindsight, I would say Laxido worked the way I expected and Dulcobalance was a disaster. Osmotic laxatives are only meant as a short-term answer to constipation and may cause serious problems if taken long-term (e.g. severe reaction to electrolyte imbalance such as seizure). That said, I wouldn't mind taken much smaller doses of Laxido to make my stool always soft. It was so easy with Laxido.

Bad reaction I had to Dulcobalance : watery itchy eyes, agitated, poor sleep, constipation, infrequent small messy stools, some flatulence, increased tenseness.

Read More

By sysbodyodor

experiment, gut dysbiosis, personal treatment

No comments

FMO3 malodor syndrome. Best papers as evidence

These 2 papers by SC Mitchell are my favorite 'evidence' of FMO3 Malodor Syndrome and the type that people will have (elusive transient form). I see trimethylamine as only a biomarker of FMO3 function and not a big player in the range of metabolites that people with FMO3 'weakness' will have.

SC Mitchell letter on Trimethylaninuria : the susceptibility of heterozygotes

Quote :

Over the past decade we have encountered many patients who have odour problems on a mild, transient, and periodic basis.3, 4 These otherwise healthy individuals are presumably heterozygotes, or compound heterozygotes, who can cope with the daily burden of trimethylamine, but have little, if any, reserve capacity when stressed by other factors and may fail to metabolically remove trimethylamine.5 To raise the general awareness of this disorder and reiterate that it “is not merely a rare recessive disorder but rather a spectrum of phenotypes of transient or mild malodour” is important,1 but it is also imperative to realise that fish-odour syndrome is not a simple genetic problem and that heterozygotes (carriers) may have to endure a transient and more elusive form of this complaint initiated by various, less obvious, and more ephemeral, factors.

Mitchell & Smith 2003 overcview of Trimethylaminuria (quote below is the main part that I use as evidence that FMO3 malodor seems a possiblity and yet no expert (including in this paper) wishes to go beyond stating TMAU)

Quote :

The intriguing question remains as to whether or not there are other endogenous or dietary substrates whose metabolism is also affected in the fish malodor syndrome. Bearing in mind that many sulfur and basic nitrogenous compounds are substrates for the enzyme system involved, this appears to be highly likely but the question remains unanswered as yet.

Read More

By sysbodyodor

fecal body odor, fmo3, gut dysbiosis, systemic body odor

No comments